MOLECULAR ONCOLOGY (MO) RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The Molecular Oncology (MO) Research Program is the basic science backbone of the Case Comprehensive Cancer Center (Case CCC). The program is home to diverse groups of basic scientists with a wide spectrum of interests that encompass contemporary cancer research. The exceptional expertise in the Program ranges from fundamental cell signaling mechanisms, to structural elucidation of macromolecules, to cancer stem cell biology and DNA damage response, tumor microenvironments, and nationally recognized disease-specific groups in brain tumors and breast cancer. The Program's overarching goal is to elucidate fundamental mechanisms of oncogenesis, encompassing the general themes of cancer stem cell regulation, DNA damage and repair, and host-tumor interactions. This is organized around 3 scientific aims: (1) Discover cancer stem cell mechanisms for cancer prevention and treatment; (2) Identify how defective DNA damage repair promotes genomic instability and alters therapeutic response and, (3) Reveal key host-tumor interactions that promote tumor progression and therapeutic resistance. These aims support the key function of the MO program to serve as an incubator to develop and nurture new research initiatives expected to mature into new research themes within the Center. The major working groups and initiatives that coalesces program members with other cancer center investigators through interprogrammatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular Cytometry, Imaging, Tissue Resources, Proteomics, and Biostatistics facilitate all aspects of member discoveries. Under the leadership of Alex Almasan (Co-Leader) and Bing-Cheng Wang (Co-Leader) the MO Program has 53 members including 44 full, 8 associate, and 1 clinical member. Members represent 18 departments and are funded with a total of $14.7M in annual research grant direct costs, $14.2M of which is peer-reviewed and $6.7M NCI-funded. Between 2012 and 2016, MO program members published 716 publications. Cancer and program related publications included 37% inter-programmatic, 19% intra-programmatic, 9% inter- and intra- programmatic and 7% that involved collaborations with another cancer center. This highly effective program has made major advances to contemporary cancer research. Examples include: discovery that glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth; elucidation that the mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma; identification of the revealed preferential iron trafficking in glioblastoma stem-like cells; examination of the control of meiotic pairing and recombination by chromosomally tethered 26S proteasome; and the discovery that glioblastoma stem cells secrete periostin to recruit tumor-associated macrophages.